M1 polarization of macrophages promotes stress-induced hair loss via interleukin-18 and interleukin-1ß.

Stress-induced hair loss is a prevalent health concern, with mechanisms that remain unclear, and effective treatment options are not yet available. In this study, we investigated whether stress-induced hair loss was related to an imbalanced immune microenvironment. Screening the skin-infiltrated immune cells in a stressed mouse model, we discovered a significant increase in macrophages upon stress induction. Clearance of macrophages rescues mice from stress-induced hair shedding and depletion of hair follicle stem cells (HFSCs) in the skin, demonstrating the role of macrophages in triggering hair loss in response to stress. Further flow cytometry analysis revealed a significant increase in M1 phenotype macrophages in mice under stressed conditions. In searching for humoral factors mediating stress-induced macrophage polarization, we found that the hormone Norepinephrine (NE) was elevated in the blood of stressed mice. In addition, in-vivo and in-vitro studies confirm that NE can induce macrophage polarization toward M1 through the ß-adrenergic receptor, Adrb2. Transcriptome, enzyme-linked immunosorbent assay (ELISA), and western blot analyses reveal that the NLRP3/caspase-1 inflammasome signaling and its downstream effector interleukin 18 (IL-18) and interleukin 1 beta (IL-1ß) were significantly upregulated in the NE-treated macrophages. However, inhibition of the NE receptor Adrb2 with ICI118551 reversed the upregulation of NLRP3/caspase-1, IL-18, and IL-1ß. Indeed, IL-18 and IL-1ß treatments lead to apoptosis of HFSCs. More importantly, blocking IL-18 and IL-1ß signals reversed HFSCs depletion in skin organoid models and attenuated stress-induced hair shedding in mice. Taken together, this study demonstrates the role of the neural (stress)-endocrine (NE)-immune (M1 macrophages) axis in stress-induced hair shedding and suggestes that IL-18 or IL-1ß may be promising therapeutic targets.

Association between HLA-B*27:04 and genetic susceptibility to ankylosing spondylitis in Hunan Province. / 湖南地区携带HLA-B*27꞉04ç­‰ä½åŸºå› äººç¾¤ä¸Žå¼ºç›´æ€§è„ŠæŸ±ç‚Žçš„æ˜“æ„Ÿæ€§å ·æœ‰å¼ºç›¸å ³æ€§ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Human leukocyte antigen (HLA) B27 is a susceptibility allele of ankylosing spondylitis (AS), and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS, but current typing methods such as sequence specific primer polymerase chain reaction (PCR-SSP) still possess limitation. Therefore, this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing (PCR-SBT). METHODS: Peripheral blood of 116 patients with suspected AS (suspected AS group) and 121 healthy volunteers (control group) admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT. Among the patients in the suspected AS group, 23 patients were finally diagnosed with AS (confirmed AS group), and the remaining 93 undiagnosed patients served as the non-confirmed AS group. PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS, and the results of the 2 methods were compared. RESULTS: The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group [11.63% vs 2.48%; P<0.001, odds ratio (OR)=5.18, 95% confidence interval (CI) 2.097 to 12.795]. B*27:04, B*27:05, B*27:06, and B*27:07 were detected in the suspected AS group and the control group. The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group (9.48% vs 1.24%; P<0.001, OR=8.346, 95% CI 2.463 to 28.282). The positive rate of B27 in the suspected AS group and the confirmed AS group (B27+/+ and B27+/-) was significantly higher than that in the control group (χ2=16.579, P<0.001; χ2=94.582, P<0.001, respectively). Among the confirmed AS group, 21 were HLA-B27 carriers, and the B27 positive rate in the confirmed AS group was 91.3%. PCR-SBT could achieve high resolution typing of the HLA-B gene locus, with higher sensitivity, specificity, positive predictive value, negative predictive value, and accuracy than PCR-SSP. CONCLUSIONS: PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province. The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

LILRB4 Checkpoint for Immunotherapy: Structure, Mechanism and Disease Targets.

LILRB4, a myeloid inhibitory receptor belonging to the family of leukocyte immunoglobulin-like receptors (LILRs/LIRs), plays a pivotal role in the regulation of immune tolerance. LILRB4 primarily mediates suppressive immune responses by transmitting inhibitory signals through immunoreceptor tyrosine-based inhibitory motifs (ITIMs). This immune checkpoint molecule has gained considerable attention due to its potent regulatory functions. Its ability to induce effector T cell dysfunction and promote T suppressor cell differentiation has been demonstrated, indicating the therapeutic potential of LILRB4 for modulating excessive immune responses, particularly in autoimmune diseases or the induction of transplant tolerance. Additionally, through intervening with LILRB4 molecules, immune system responsiveness can be adjusted, representing significant value in areas such as cancer treatment. Thus, LILRB4 has emerged as a key player in addressing autoimmune diseases, transplant tolerance induction, and other medical issues. In this review, we provide a comprehensive overview of LILRB4, encompassing its structure, expression, and ligand molecules as well as its role as a tolerance receptor. By exploring the involvement of LILRB4 in various diseases, its significance in disease progression is emphasized. Furthermore, we propose that the manipulation of LILRB4 represents a promising immunotherapeutic strategy and highlight its potential in disease prevention, treatment and diagnosis.

Evaluation of Right Ventricular Global Longitudinal Function in Patients with Tetralogy of Fallot by Two-dimensional Ultrasound Speckle Tracking Imaging / 华中科技大学学报（医学）（英德文版）

Quantification of right ventricular(RV)volume and function remains a challenge because of RV complex geometry by conventional echocardiography.The purpose of this study was to assess RV global longitudinal function in patients with tetralogy of Fallot(TOF)by 2-dimensional ultrasound speckle tracking imaging(STI).Thirty-eight patients with TOF were enrolled in this study and divided into child group(n=25)and adult group(n=13)according to age.Thirty-eight age-and sex-matched normal subjects were selected as control groups including child control group(n=25)and adult control group(n=13).RV global longitudinal peak systolic strain(GLS),strain rate(GLSPs),early diastolic strain rate(GLSRe)and late diastolic strain rate(GLSRa)were measured in all subjects by STI from the apical 4-chamber view and compared between groups.Furthermore,the main factors affecting the RV global longitudinal functional parameters were assessed.Compared with those in controls,RV GLS,GLSRs and GLSPe were significantly reduced in patients with TOF(P<0.05 for all).RV GLSRs was significantly decreased in adult patients with TOF as compared with that in child patients(P<0.05).There was no significant difference in RV GLS,GLSRe and GLSRa between child and adult TOF groups(P>0.05).The diameter of right ventricle,main pulmonary artery and ventricular septum defect had correlations with RV GLSRs(r1=-0.490,r2=0.580,r3=-0.528,respectively,P<0.05 for all).Tricuspid annular plane peak systolic velocity(Sm)was the independent predictor of RV global strain and strain rate(β1=0.355,P1=0.031,β2=0.307,P2=0.021).RV global longitudinal function is decreased in patients with TOF,especially in adult patients.STI is a sensitive and accurate technique in RV global functional assessment.

Assessment of Regional Left Ventricular Myocardial Function in Rats after Acute Occlusion of Left Anterior Descending Artery by Two-dimensional Speckle Tracking Imaging / 华中科技大学学报（医学）（英德文版）

This study evaluated the change in regional left ventricular myocardial function in rats following acute occlusion of the left anterior descending coronary artery (LAD) by using two-dimensional speckle tracking imaging (2D-STI). Sixty Wistar rats were randomly divided into two groups,a myocardial infarction (MI) group,in which 50 rats were subjected to LAD occlusion for 30-45 min,and a sham-operated (SHAM) group that contained 10 rats serving as control. Echocardiography was performed at baseline and 1,4 and 8 week(s) after the operation. High frequency two-dimensional images of left ventricular short axis at papillary muscle level were recorded. Peak systolic radial strain (PRS) and circumferential strain (PCS) were measured in the mid-ventricle in short-axis view by using EchoPAC workstation. Left ventrieular internal diameter at diastole (LVIDd)and systole (LVIDs),fractional shortening (FS),ejection fraction (EF) and left ventricular mass (LVM)were measured by anatomical M-model echocardiography. Infarct size was measured using triphenyl tetrazolium chloride (TTC) staining 1 week and 8 weeks after the operation. Fibrosis of left ventricular myocardium was displayed using Van Gieson staining 1 week after the infarction. In terms of the TTC staining results,the left ventricle fell into three categories:infarcted,peri-infarcted and remote myocardial regions. Compared with those at baseline and in the SHAM group,(1) PRS and PCS in the infarcted,peri-infarcted and remote myocardial regions were significantly decreased in the MI group within 1 week after the operation (P＜0.05) and the low levels lasted 8 weeks;(2) Compared with those at baseline,LVIDd,LVIDs,FS,EF and LVM in the MI group showed no significant difference 1 week after the operation (P＞0.05). However,LVIDd,LVIDs and LVM were increased significantly 4 and 8 weeks after the operation (P＜0.05),and FS and EF were decreased substantially (P＜0.05). Van Gieson staining showed that fibrosis developed in all the three myocardial regions to varying degrees. It is concluded that 2D-STI is non-invasive and can be used to assess regional function of myoeardium with different blood supply in rats following acute occlusion of the LAD,and can be used as a sensitive and reliable means to follow up the process of left ventricular remodeling.

Quantitative Analysis of Myocaridal Perfusion in Rabbits by Tansthoracic Real-time Myocardial Contrast Echocardiography / 华中科技大学学报（医学）（英德文版）

To evaluate the feasibility of real-time myocardial contrast echocardiography (RTMCE) by quantitative analysis of myocardial perfusion in rabbits,transthoracic RTMCE was performed in 10 healthy rabbits by using continuous infusion of Sono Vue into the auricular vein. The short axis view at the papillary muscle level was obtained. The duration of the time that the contrast took to appear in right heart,left heart and myocardium was recorded. The regional myocardial signal intensity (SI) versus refilling time plots were fitted to an exponential function:y(t) =A(1-e-β(t-t0)) + C,where y is SI at any given time,A is the SI plateau that reflects myocardial blood volume,and β is the slope of the refilling curve that reflects myocardial microbubble velocity. The A,β and A×β values at different infusion rate of SonoVue were analyzed and the A,β and A×β values in each segment in the short axis view at the papillary muscle level were compared. All the animal experiments were successful and high-quality images were obtained. The best intravenous infusion rate for Sono Vue was 30 mL/h. The contrast appeared in fight heart,left heart and myocardium at 7.5±2.2 s,9.1±2.4 s and 12.2±1.6 s respectively. After 16.6±2.3s,myocardial opacification reached a steady state. The mean A,β and A×β value in the short axis view at the papillary muscle level were 9.8±3.0 dB,1.4±0.5 s 1 and 13.5±3.6 dB×s-1 respectively.A,β and A×β values showed no significant differences among 6 segments. It was suggested that RTMCE was feasible for quantitative analysis of myocardial perfusion in rabbits. It provides a non-invasive method to evaluate the myocardial perfusion in rabbit disease models.

Ultrasound Speckle Tracking Imaging Contributes to Early Diagnosis of Impaired Left Ventricular Systolic Function in Patients with Type 2 Diabetes Mellitus / 华中科技大学学报（医学）（英德文版）

To investigate the value of ultrasound speckle tracking imaging (STI) in the assessment of the short-axis and long-axis systolic function of the left ventricle (LV) in patients with type 2 diabetes mellitus (DM), 100 subjects with normal ejection fraction were studied, including 41 patients with DM only (DM group), 22 patients with both DM and left ventricular hypertrophy (DH group),and 37 healthy subjects (control group). Left ventricle systolic function in the long axis defined as longitudinal strain, and that in the short axis defined as radial strain, apical and basal LV rotations,and LV twist were assessed respectively. The results showed that average peak strain in the long axis at basal, middle and apical levels, and global peak strain were significantly decreased in the patient groups when compared with the control group (P<0.001 for each). The parameters in DH group were significantly lower than those in DM group (P<0.01 for each). There were no significant differences in average radial peak strain in the short axis at different levels, and global peak strain among the three groups (P>0.05). Apical and basal LV rotations, and LV twist were greater in the patient groups than in the control group (P<0.01 for each). Basal LV rotation and LV twist were greater in DH group than those in DM group (P<0.01). It was concluded that STI may be used to identify early abnormalities in patients with type 2 DM that have normal left ventricular systolic function.